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Non-Hodgkin’s Lymphoma

A Review of Immunotherapeutic Approaches to Treatment

  • Review Articles
  • Immunology-Based Agents
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Summary

Non-Hodgkin’s lymphomas (NHL) represent a heterogenous group of diseases including low, intermediate and high grade histological subtypes. Most entities are sensitive to chemotherapy and radiotherapy. However, most relapsed patients are incurable with conventional treatment. The major reason for unsatisfactory long-term results in NHL is tumour cells that persist after standard treatment. New sensitive techniques have been developed to detect occult lymphoma cells. These cells might be eradicated by new immunotherapeutic agents with different modes of action, such as cytokines or antibody-based agents. In NHL, most experience has been accumulated with interferon-α, which seems to be effective against minimal residual disease (MRD). The experience with interleukin-2 and interleukin-3 is less convincing. Monoclonal antibodies have been used in their native form, or conjugated with radioisotopes or toxins to selectively destroy lymphoma cells. Such immunotoxins and radioisotope-coupled antibodies have shown promising results in early clinical trials, and are now being evaluated in patients with smaller tumour burdens.

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References

  1. Fisher RI, Gaynor ER, Dahlberg S, et al. Comparison of standard regimens (HOP) with three intensive chemotherapy regimens for advanced non-Hodgkin’s lymphoma. N Engl J Med 1993; 328: 1002–6

    PubMed  CAS  Google Scholar 

  2. Colombat P, Gorin NC, Lemonnier MP, et al. The role of autologous bone marrow transplantation in 46 adult patients with non-Hodgkin’s lymphoma. J Clin Oncol 1990; 6: 630–7

    Google Scholar 

  3. Phillips GL, Shepherd JD, Barnett MJ, et al. Busulfan, cyclo-phosphamide, and melphalan conditioning for autologous bone marrow transplantation in hematologic malignancies. J Clin Oncol 1991; 9: 1880–8

    PubMed  CAS  Google Scholar 

  4. Gianni AM, Bregni M, Siena S, et al. 5-year update of the Milan cancer institute randomized trial of high-dose sequential (HDS) vs MACOP-B therapy for diffuse large cell lymphomas [abstract]. Proc Am Soc Clin Oncol 1994; 13: 1263

    Google Scholar 

  5. Köhler G, Milstein C. Continuous cultures of fused cells secreting antibody of pre-defined specificity. Nature 1975; 256: 495–7

    PubMed  Google Scholar 

  6. Hagenbeek A, Martens ACM. Cryopreservation of autologous marrow grafts in acute leukemia: survival of in vivo clonoge-nic leukemic cells and normal hematopoietic stem cells. Leukemia 1989; 3: 535–7

    PubMed  CAS  Google Scholar 

  7. Gribben JG, Freedman AS, Neuberg D, et al. Immunologic purging of marrow assessed by PCR before autologous bone marrow transplantation for B-cell lymphoma. N Engl J Med 1991; 325: 1525–33

    PubMed  CAS  Google Scholar 

  8. Gribben JG, Freedman AS, Woo SD, et al. All advanced stage non-Hodgkin’s lymphomas with a polymerase chain reaction amplifiable breakpoint of bcl-2 have residual cells containing the bcl-2 rearrangement at evaluation and after treatment. Blood 1991; 78: 3275–80

    PubMed  CAS  Google Scholar 

  9. Sharp JG, Joshi SS, Armitage JO, et al. Significance of detection of occult non-Hodgkin’s lymphoma in histologically uninvolved bone marrow by a culture technique. Blood 1992; 79: 1074–80

    PubMed  CAS  Google Scholar 

  10. Campana D, Pui CH. Detection of minimal residual disease in acute leukemia: methodologie advances and clinical significance. Blood 1995; 85: 1416–34

    PubMed  CAS  Google Scholar 

  11. Cueno A, Wlodarska I, Aly MS, et al. Non-radioactive in situ hybridization for the detection of trisomy 12 in B-cell chronic lymphocytic leukemia. Br J Haematol 1992; 81: 192–6

    Google Scholar 

  12. Campana D, Coustan-Smith E, Behm FG. The definition of remission in acute leukemia with immunologie methods. Bone Marrow Transplant 1991; 8: 429–37

    PubMed  CAS  Google Scholar 

  13. Sharp JG, Mann SL, Murphy B, et al. Culture methods for the detection of minimal tumor contamination of hematopoietic harvests: a review. J Hematother 1995; 4: 141–8

    PubMed  CAS  Google Scholar 

  14. Drexler HG, Borkhardt A, Janssen JWG. Detection of chromosomal translocations in leukemia-lymphoma cells by polymerase chain reaction. Leuk Lymphoma 1995; 19: 359–80

    PubMed  CAS  Google Scholar 

  15. Gribben JG, Neuberg D, Barber M, et al. Detection of residual lymphoma cells by polymerase chain reaction in peripheral blood is significantly less predictive for relapse than detection in bone marrow. Blood 1994; 83: 3800–7

    PubMed  CAS  Google Scholar 

  16. Negrin RS, Pesando J, Long GD, et al. Comparison of tumor cell contamination of ‘purged’ bone marrow to peripheral blood mononuclear cells assessed by PCR in non-Hodgkin’s lymphoma [abstract]. Blood 1992; 80: 235

    Google Scholar 

  17. Waldmann TA. The interleukin-2 receptor. J Biol Chem 1991; 266: 2681–4

    PubMed  CAS  Google Scholar 

  18. Taniguchi T, Minami Y. The IL-2/IL-2 receptor system: a current overview. Cell 1993; 73: 5–8

    PubMed  CAS  Google Scholar 

  19. Kreitman RJ, Pastan I. Recombinant single-chain immunotoxins against T and B cell leukemias. Leuk Lymphoma 1994; 13: 1–10

    PubMed  CAS  Google Scholar 

  20. Taniguchi T, Matsui H, Fujita T, et al. Structure and expression of a cloned cDNA for human interleukin-2. Nature 1983; 302: 305–10

    PubMed  CAS  Google Scholar 

  21. Oshimi K, Oshimi Y, Akutsu M, et al. Cytotoxicity of IL-2 activated lymphocytes for leukemia and lymphoma cells. Blood 1986; 68: 938–48

    PubMed  CAS  Google Scholar 

  22. Lafreniere R, Rosenberg SA. Successful immunotherapy of murine hepatic experimental metastasis with lymphokine activated killer cells and recombinant interleukin-2. Cancer 1985; 45: 3735–41

    CAS  Google Scholar 

  23. Rosenberg SA, Lotze MT, Muul LM, et al. Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med 1985; 313: 1485–92

    PubMed  CAS  Google Scholar 

  24. Gisselbrecht C, Maraninchi D, Pico JL, et al. Interleukin-2 treatment in lymphoma: a phase II multicenter study. Blood 1994; 83: 2081–5

    PubMed  CAS  Google Scholar 

  25. Tourani JM, Levy V, Briere J, et al. Interleukin-2 therapy for refractory and relapsing lymphomas. Eur J Cancer 1991; 12: 1676–80

    Google Scholar 

  26. Allison MA, Jones SE, McGuffy P. Phase I trial of outpatient interleukin-2 in malignant lymphoma, chronic lymphocytic leukemia, and selected solid tumors. J Clin Oncol 1989; 7: 75–80

    PubMed  CAS  Google Scholar 

  27. Bernstein ZP, Vaickus L, Friedman N, et al. Interleukin-2 lymphokine-activated killer cell therapy of non-Hodgkin’s lymphoma and Hodgkin’s disease. J Immunother 1991; 10: 141–6

    PubMed  CAS  Google Scholar 

  28. Weber JS, Yang JC, Topalian SL, et al. The use of interleukin-2 and lymphokine activated killer cells for treatment of patients with non-Hodgkin’s lymphoma. J Clin Oncol 1992; 10: 33–40

    PubMed  CAS  Google Scholar 

  29. Duggan DB, Santarelli MT, Zamkoff K, et al. A phase II study of recombinant interleukin-2 with or without recombinant interferon-β in non-Hodgkin’s lymphoma. A study of the Cancer and Leukemia group B. J Immunother 1992; 10: 115–22

    Google Scholar 

  30. Margolin KA, Aronson FR, Sznol M, et al. Phase II trial of high-dose interleukin-2 and lymphokine-activated killer cells in Hodgkin’s disease and non-Hodgkin’s lymphoma. J Immunother 1991; 10: 214–20

    PubMed  CAS  Google Scholar 

  31. Blaise D, Olive D, Stoppa AM, et al. Hematologic and immunologic effects of the systemic administration of recombinant interleukin-2 after autologous bone marrow transplantation. Blood 1990; 76: 1092–7

    PubMed  CAS  Google Scholar 

  32. Benyunes MC, Massumoto C, York A, et al. Interleukin-2 with or without lymphokine-activated killer cells are consolidative immunotherapy after autologous bone marrow transplantation for acute myelogenous leukemia. Bone Marrow Transplant 1993; 12: 159–63

    PubMed  CAS  Google Scholar 

  33. Nagler A, Ackerstein A, Or R, et al. Immunotherapy with recombinant human interleukin-2 and recombinant interferon-alpha in lymphoma patients postautologous marrow or stem cell transplantation. Blood 1997; 89: 3951–9

    PubMed  CAS  Google Scholar 

  34. Lauria F, Raspadori D, Ventura MA, et al. Immunologie and clinical modifications following low-dose subcutaneous administration of rIL-2 in non-Hodgkin’s lymphoma patients after autologous bone marrow transplantation. Bone Marrow Transplant 1996; 18: 79–85

    PubMed  CAS  Google Scholar 

  35. Benyunes MC, Higuchi C, York A, et al. Immunotherapy with interleukin-2 with or without lymphokine-activated killer cells after autologous bone marrow transplantation for malignant lymphoma: a feasibility trial. Bone Marrow Transplant 1995; 16: 283–8

    PubMed  CAS  Google Scholar 

  36. DeNardo SJ, DeNardo GL, O’Grady LF, et al. Fractionated radioimmunotherapy of B-cell malignancies with 131I LYM-1. Cancer Res 1990; 50: 1014–6S

    Google Scholar 

  37. Ganser A, Lindemann A, Seipelt G, et al. Effects of recombinant human IL-3 in patients with normal hematopoiesis and in patients with bone marrow failure. Blood 1990; 76: 666–76

    PubMed  CAS  Google Scholar 

  38. Clayberger C, Luna-Fineman S, Lee JE, et al. Interleukin-3 is a growth factor for human follicular B cell lymphoma. J Exp Med 1992; 175: 371–6

    PubMed  CAS  Google Scholar 

  39. Younes A, Drach J, Katz R, et al. Growth inhibition of follicular small-cleaved cell lymphoma cells in short term culture by IL-3. Ann Oncol 1994; 5: 265–8

    PubMed  CAS  Google Scholar 

  40. Younes A, Sarris A, Consoli U, et al. A pilot study of high-dose interleukin-3 treatment of relapsed follicular small cleaved-cell lymphoma: hematologic, immunologie and clinical results. Blood 1996; 87: 1698–703

    PubMed  CAS  Google Scholar 

  41. Baron S, Tyring SK, Fleischmann R, et al. The interferons: mechanism of action and clinical applications. JAMA 1991; 266: 1375–83

    PubMed  CAS  Google Scholar 

  42. Einat M, Resnitzky D, Kimchi A. Close link between reduction of c-myc expression by interferon and G0/G1 arrest. Nature 1985; 313: 597–600

    PubMed  CAS  Google Scholar 

  43. Horning SJ, Merigan TE, Krown SE, et al. Human interferon alpha in malignant lymphoma and Hodgkin’s disease. Cancer 1985; 56: 74–87

    Google Scholar 

  44. Quesada JR, Reuben J, Manning JT, et al. Alpha interferon for induction of remission in hairy cell leukemia. N Engl J Med 1984; 310: 15–28

    PubMed  CAS  Google Scholar 

  45. Gilewski TA, Richards JM. Biologic response modifiers in non-Hodgkin’s lymphomas. Semin Oncol 1990; 17: 74–87

    PubMed  CAS  Google Scholar 

  46. Aviles A, Duque G, Talavera A, et al. Interferon alpha 2b as maintenance therapy in low-grade malignant lymphoma improves duration of remission and survival. Leuk Lymphoma 1996; 20: 495–9

    PubMed  CAS  Google Scholar 

  47. Tedder TF, Engel P. CD20: a regulator of cell-cycle progression and B lymphocytes. Immunol Today 1994; 15: 450–4

    PubMed  CAS  Google Scholar 

  48. Yao XR, Scott DW. Expression of protein tyrosine kinases in the Ig complex of anti-mu-sensitive and anti-mu-resistant B-cell lymphomas: role of the p55blk kinase in signaling growth arrest and apoptosis. Immunol Rev 1993; 132: 163–86

    PubMed  CAS  Google Scholar 

  49. Meeker TC, Lowder J, Maloney DG, et al. A clinical trial of anti-idiotype therapy for B cell malignancy. Blood 1995; 65: 1349–63

    Google Scholar 

  50. Brown SL, Miller RA, Horning SJ, et al. Treatment of B-cell lymphomas with anti-idiotype antibodies alone and in combination with alpha interferon. Blood 1989; 73: 651–61

    PubMed  CAS  Google Scholar 

  51. Vuist WMJ, Levy R, Maloney DG. Lymphoma regression induced by monoclonal.anti-idiotypic antibodies correlates with their ability to induce Ig signal transduction and is not prevented by their tumor expression of high levels of Bcl-2 protein. Blood 1994; 83: 899–906

    PubMed  CAS  Google Scholar 

  52. Hale G, Dyer MJS, Clark MR, et al. Remission induction in non-Hodgkin lymphoma with reshaped human monoclonal antibody Campath-1H. Lancet 1988; 2: 1394–9

    PubMed  CAS  Google Scholar 

  53. Lim SH, Davey G, Marcus R. Differential response in a patient treated with Campath-1H monoclonal antibody for refractory non-Hodgkin’s lymphoma. Lancet 1993; 341: 432–3

    PubMed  CAS  Google Scholar 

  54. Rai KR, Hoffman M, Janson D, et al. Immunosuppression and opportunistic infections (OI) in patients with chronic lymphocytic leukemia (CLL) following Campath 1-H therapy [abstract]. Blood 1995; 10 Suppl.: 1381

    Google Scholar 

  55. Anagnostopoulos A, Fassas A, Papaminas N, et al. Immunotherapy with Campath-1H for patients with lymphoproliferative isease [abstract]. Blood 1995; 10 Suppl.: 3297

    Google Scholar 

  56. Österborg A, Fassa A, Anagnostopoulos A, et al. Humanized CD52 monoclonal antibody Campath-1H as first-line treatment in chronic lymphocytic leukaemia. Br J Haematol 1996; 93: 151–3

    PubMed  Google Scholar 

  57. Maloney DG, Liles TM, Czerwinski DK, et al. Phase I clinical trial using escalating single-dose infusion of chimeric anti-CD20 monoclonal antibody (IDEC-C2B8) in patients with recurrent B-cell lymphoma. Blood 1994; 84: 2457–66

    PubMed  CAS  Google Scholar 

  58. Maloney DG, Grillo-Lopez AJ, Bodkin D, et al. IDEC-C2B8 anti-CD20 antibody: results of long term follow-up of relapsed NHL phase II trial patients [abstract]. Blood 1995; 10 Suppl.: 205

    Google Scholar 

  59. Durandy A, Brousse N, Rozenberg F, et al. Control of human B cell tumor growth in severe combined immunodeficiency mice by monoclonal anti-B cell antibodies. J Clin Invest 1992; 90: 945–52

    PubMed  CAS  Google Scholar 

  60. Klein E, Klein G, Nadkarni JS, et al. Surface IgM-kappa specificity on a Burkitt lymphoma cell in vivo and in derived culture lines. Cancer Res 1968; 28: 1300–10

    PubMed  CAS  Google Scholar 

  61. Milstein C, Cuello AC. Hybrid hybridomas and their use in immunohistochemistry. Nature 1983; 305: 537–41

    PubMed  CAS  Google Scholar 

  62. French RR, Hamblin TJ, Bell AJ, et al. Treatment of B-cell lymphomas with combination of bispecific antibodies and saporin. Lancet 1995; 346: 223–4

    PubMed  CAS  Google Scholar 

  63. Somasundaram C, Matzku S, Schuhmacher J, et al. Development of a bispecific monoclonal antibody against a gallium-67 chelate and the human melanoma-associated antigen p97 for potential use in pretargeted immunoscintigraphy. Cancer Immunol Immunother 1993; 36: 337–45

    PubMed  CAS  Google Scholar 

  64. Fanger MW, Shen L, Graziano RF, et al. Cytotoxicity mediated by human Fc receptors for IgG. Immunol Today 1989; 10: 92–7

    PubMed  CAS  Google Scholar 

  65. Schmidt M, Hynes NE, Groner B, et al. A bivalent single-chain antibody-toxin specific for ErbB-2 and the EGF receptor. Int J Cancer 1996; 65: 538–46

    PubMed  CAS  Google Scholar 

  66. Holliger P, Prospero T, Winter G. Diabodies: small bivalent and bispecific antibody fragments. Proc Natl Acad Sci USA 1993; 90: 6444–8

    PubMed  CAS  Google Scholar 

  67. Pack P, Kujau M, Schroeckh V, et al. Improved bivalent miniantibodies, with identical avidity as whole antibodies, produced by high cell density fermentation of Escherichia coli. Biotechnology 1993; 11: 1271–7

    PubMed  CAS  Google Scholar 

  68. de Kruif J, Logtenberg T. Leucine zipper dimerized bivalent and bispecific scFv antibodies from a semi-synthetic antibody phage display library. J Biol Chem 1996; 271: 7630–4

    PubMed  Google Scholar 

  69. Perez P, Hoffman RW, Shaw S. Specific targeting of cytotoxic T cells by anti-T3 conjugates. Nature 1985; 316: 354–6

    PubMed  CAS  Google Scholar 

  70. June CH, Ledbetter JA, Linsley P, et al. Role of the CD28 receptor in T-cell activation. Immunol Today 1990; 11: 211–6

    PubMed  CAS  Google Scholar 

  71. Segal DM, Garrido MA, Perez P, et al. Targeted cytotoxic cells s a novel form of cancer immunotherapy. Mol Immunol 1988; 25: 1099–103

    PubMed  CAS  Google Scholar 

  72. Jung G, Ledbetter JA, Mueller-Eberhard HJ. Induction of cytotoxicity in resting human T lymphocytes bound to tumor cells by antibody heteroconjugates. Proc Natl Acad Sci USA 1987; 84: 4611–5

    PubMed  CAS  Google Scholar 

  73. Nijhuis EW, Wiel-Van Kemenade E, Figdor CG, et al. Activation and expansion of tumor-infiltrating lymphocytes by anti-CD3 and anti-CD28 monoclonal antibodies. Cancer Immunol Immunother 1990; 32: 245–50

    PubMed  CAS  Google Scholar 

  74. Haagen IA, Geerars A, de Lau WBM, et al. The efficacy of CD3 x CD 19 bispecific monoclonal antibody (BsAb) in a clonogenic assay: the effect of repeated addition of BsAb and interleukin-2. Blood 1995; 85: 3208–12

    PubMed  CAS  Google Scholar 

  75. Bohlen H, Hopff T, Manzke O, et al. Lysis of malignant B cells from patients with B-chronic lymphocytic leukemia by autologous T cell activated with CD3 x CD 19 bispecific antibodies in combination with bivalent CD28 antibodies. Blood 1993; 82: 1803–12

    PubMed  CAS  Google Scholar 

  76. Bohlen H, Manzke O, Patel B, et al. Cytolysis of leukemic B-cells by T-cells activated via two bispecific antibodies. Cancer Res 1993; 53: 4310–4

    PubMed  CAS  Google Scholar 

  77. De Gast GC, van Houten AA, Haagen IA, et al. Clinical experience with CD3 x CD 19 bispecific antibodies in patients with B cell malignancies. J Hematother 1995; 4: 433–7

    PubMed  Google Scholar 

  78. Ely P, Wallace PK, Givan AL, et al. Bispecific-armed, interferon-primed macrophage-mediated phagocytosis of malignant non-Hodgkin’s lymphoma. Blood 1996; 87: 3813–21

    PubMed  CAS  Google Scholar 

  79. Endo Y, Tsurugi K. RNA N-glycosidase activity of ricin A-chain: mechanism of action of the toxic lectin ricin on eu-karyotic ribosomes. J Biol Chem 1987; 262: 8128–30

    PubMed  CAS  Google Scholar 

  80. Lewis MS, Youle RJ. Ricin subunit association: thermodynamics and the role of the disulfide bond in toxicity. J Biol Chem 1986; 261: 11571–7

    PubMed  CAS  Google Scholar 

  81. Lambert JM, McIntyre G, Gauthier MN, et al. The galactose binding sites of the cytotoxic lectin ricin can be chemically blocked in high yield with reactive ligands prepared by chemical modifications of glycopeptides containing triantennary N-linked Oligosaccharides. Biochemistry 1991; 30: 3234–47

    PubMed  CAS  Google Scholar 

  82. Eiklid K, Olsnes S, Pihl A. Entry of lethal doses of abrin, ricin and modeccin into the cytosol of HeLa cells. Exp Cell Res 1980; 126: 321–6

    PubMed  CAS  Google Scholar 

  83. Greenfield L, Bjorn MJ, Horn G, et al. Nucleotide sequence of the structural gene for diphtheria toxin carried by corynebacteriophage beta. Proc Natl Acad Sci USA 1983; 80: 6853–7

    PubMed  CAS  Google Scholar 

  84. Carroll SF, Collier RJ. NAD binding site of diphtheria toxin: identification of a residue within nicotinamide subsite by photochemical modification with NAD. Proc Natl Acad Sci USA 1984; 81: 3307–11

    PubMed  CAS  Google Scholar 

  85. FitzGerald D, Pastan I. Targeted toxin therapy for the treatment of cancer. J Natl Cancer Inst 1989; 81: 1455–63

    PubMed  CAS  Google Scholar 

  86. Soler-Rodriguez AM, Ghetie MA, Oppenheimer-Marks N, et al. Ricin A-chain and ricin A-chain immunotoxins rapidly damage human endothelial cells: implication for vascular leak syndrome. Exp Cell Res 1993; 206: 227–34

    PubMed  CAS  Google Scholar 

  87. Grossbard ML, Freedman AS, Ritz J, et al. Serotherapy of B-cell neoplasms with anti-B4-blocked ricin: a phase-I trial with daily bolus infusion. Blood 1992; 79: 576–85

    PubMed  CAS  Google Scholar 

  88. Grossbard ML, Lambert JM, Goldmacher VS, et al. Anti-B4-blocked ricin: a phase I trial of 7-day continuous infusion in patients with B-cell neoplasms. J Clin Oncol 1993; 11: 726–37

    PubMed  CAS  Google Scholar 

  89. Grossbard ML, Gribben JG, Freedman AS, et al. Adjuvant immunotoxin therapy with anti-B4-blocked ricin after autologous bone marrow transplantation for patients with B-cell non-Hodgkin’s lymphoma. Blood 1993; 81: 2263–71

    PubMed  CAS  Google Scholar 

  90. Williams DP, Parker K, Bacha P, et al. Diphtheria toxin receptor binding domain substitution with interleukin-2: genetic construction and properties of a diphtheria toxin-related interleukin-2 fusion protein. Protein Eng 1987; 1: 493–8

    PubMed  CAS  Google Scholar 

  91. Williams DP, Snider CE, Strom TB, et al. Structure/function analysis of interleukin-2 toxin (DAB486IL-2). J Biol Chem 1990; 265: 11885–9

    PubMed  CAS  Google Scholar 

  92. LeMaistre CF, Craig FE, Meneghetti C, et al. Phase I trial of a 90-minute infusion of the fusion toxin DAB486IL-2 in hematologie cancers. Cancer Res 1993; 53: 3930–4

    PubMed  CAS  Google Scholar 

  93. LeMaistre CF, Meneghetti C, Rosenblum M, et al. Phase I trial of an interleukin-2 (IL-2) fusion toxin (DAB486IL-2) in hematologie malignancies expressing the IL-2 receptor. Blood 1992; 79: 2547–54

    PubMed  CAS  Google Scholar 

  94. Foss F, Nichols J, Parker K, Seragen Lymphoma Study Group. Phase I/II trial of DAB389IL-2 in patients with NHL, HD and CTCL. Abstracts of the Fourth International Symposium on Immunotoxins 1995: 1995 Jun 8–10: Myrtle Beach (FL): 159

  95. Eary JF, Krohn KA, Kishore R, et al. Radiochemistry haloge-nated antibodies. In: Zalutsky M, editor. Antibodies in radio- diagnosis and therapy. Boca Raton (FL): CRC Press, 1989: 84–102

    Google Scholar 

  96. Rhodes BA, Zamora PA, Newell KD, et al. Tc-99m labeling of murine monoclonal antibody fragments. J Nucl Med 1986; 27: 685–93

    PubMed  CAS  Google Scholar 

  97. Zimmer AM, Spies SM. New approaches to radiolabeling monoclonal antibodies. In: Rosen ST, Kuzel TM, editors. Immunoconjugate therapy of hematologic malignancies. Dordrecht: Kluwer Academic Publishers, 1993: 100–9

    Google Scholar 

  98. DeNardo SJ, DeNardo GL, O’Grady LF, et al. Pilot study of radioimmunotherapy of B cell lymphoma and leukemia using 131I LYM-1 monoclonal antibody. Antibody Immunoconjugates Radiopharm 1988; 1: 17–33

    Google Scholar 

  99. DeNardo SJ, DeNardo GL, O’Grady LF, et al. Treatment of B-cell malignancies with 131I LYM-1 monoclonal antibodies. Int J Cancer 1988; 40: 96–101

    Google Scholar 

  100. Kuzel T, Rosen ST, Zimmer AM, et al. A phase I escalating-dose safety, dosimetry and efficacy study of radiolabeled monoclonal antibody LYM-1. Cancer Biother 1993; 8: 3–16

    PubMed  CAS  Google Scholar 

  101. Kaminski MS, Fig LM, Zasadny KR, et al. Imaging, dosimetry, and radioimmnotherapy with iodine 131-labeled anti-CD37 antibody in B-cell lymphoma. J Clin Oncol 1992; 10: 1696–711

    PubMed  CAS  Google Scholar 

  102. Czuczman MS, Strauss DJ, Divgi CR, et al. Phase I dose escalation trial of iodine 131-labeled monoclonal antibody OKB7 in patients with non-Hodgkin’s lymphoma. J Clin Oncol 1993; 11: 2021–8

    PubMed  CAS  Google Scholar 

  103. Goldenberg DM, Horowitz JA, Sharkey RM, et al. Targeting, dosimetry, and radioimmunotherapy of B-cell lymphoma with iodine-131-labeled LL2 monoclonal antibody. J Clin Oncol 1991; 9: 548–64

    PubMed  CAS  Google Scholar 

  104. Juweid M, Sharkey RM, Markowitz A, et al. Treatment of non- Hodgkin’s lymphoma with radiolabeled murine, chimeric, or humanized LL2, an anti-CD22 monoclonal antibody. Cancer Res 1995; 55: 5899–907S

    Google Scholar 

  105. Kaminski MS, Zasadny KR, Francis IR, et al. Iodine-131-anti-B1 radioimmunotherapy for B-cell lymphoma. J Clin Oncol 1996; 14: 1974–81

    PubMed  CAS  Google Scholar 

  106. Press OW, Eary J, Appelbaum FR, et al. Radiolabeled antibody therapy of lymphoma. In: Dana B, editor. Malignant lymphomas, including Hodgkin’s disease: diagnosis, management, and clinical problems. Boston: Kluwer Academic Press, 1993: 127–45

    Google Scholar 

  107. Press OW, Eary JF, Appelbaum FR, et al. Phase II trial of 131I-Bi (anti-CD20) antibody therapy with autologous stem cell transplantation for relapsed B cell lymphomas. Lancet 1995; 346: 336–40

    PubMed  CAS  Google Scholar 

  108. Press OW, Eary JF, Appelbaum FR, et al. Radiolabeled-antibody therapy of B-cell lymphoma with autologous bone marrow support. N Engl J Med 1993; 329: 1219–24

    PubMed  CAS  Google Scholar 

  109. White CA, Halpern SE, Parker BA, et al. Radioimmunotherapy of relapsed B-cell lymphoma with yttrium-90 anti-idiotype monoclonal antibodies. Blood 1996; 87: 3640–9

    PubMed  CAS  Google Scholar 

  110. Greene MI. Cellular and genetic basis of immune reactivity to tumor cells. Contemp Top Mol Immunol 1980; 11: 81–7

    CAS  Google Scholar 

  111. Howie SM, McBride WH. Tumor-specific T-helper activity can be abrogated by two distinct suppressor-cell mechanisms. Eur J Immunol 1982; 12: 671–5

    PubMed  CAS  Google Scholar 

  112. Jerne N. Towards a network theory of the immune system. Ann Immunol 1974; 125: 373–89

    CAS  Google Scholar 

  113. Mittelman A, Chen ZJ, Yang H, et al. Human high molecular weight melanoma associated antigen (HMW-MAA) mimicry by mouse anti-id-idiotypic monoclonal antibody MK2-23: induction of humoral anti-HMW-MAA immunity and prolongation of survival in patients with stage IV melanoma. Proc Natl Acad Sci USA 1992; 89: 466–70

    PubMed  CAS  Google Scholar 

  114. Pohl C, Denfeld R, Renner C, et al. CD30-antigen-specific targeting and activation of T cells via murine bispecific monoclonal antibodies against CD3 and CD28: potential use for the treatment of Hodgkin’s lymphoma. Int J Cancer 1993; 54: 820–7

    PubMed  CAS  Google Scholar 

  115. Pohl C, Renner C, Schwonzen M, et al. CD30-specific AB1- AB2-AB3 internal image antibody network: potential use as anti-idiotype vaccine against Hodgkin’s lymphoma. Int J Cancer 1993; 54: 418–25

    PubMed  CAS  Google Scholar 

  116. Schobert I, Renner C, Pfreundschuh M, et al. Mimicry of the Hodgkin-associated IRac antigen by an anti-idiotype network: potential use in active immunotherapy of Hodgkin’s lymphoma. Leuk Lymphoma 1994; 13: 429–40

    PubMed  CAS  Google Scholar 

  117. Seon BK, Negoro S, Barcos MP, et al. Monoclonal antibody SN2 defining a human T-cell leukemia-associated cell surface glycoprotein. J Immunol 1984; 132: 2089–95

    PubMed  CAS  Google Scholar 

  118. Foon KA, Oseroff AR, Vaickus L, et al. Immune response in patients with T-cell lymphoma treated with an anti-idiotype antibody mimicking a highly restricted T-cell antigen. Clin Cancer Res 1995; 1: 1285–94

    PubMed  CAS  Google Scholar 

  119. Kwak LW, Campbell MJ, Czerwinski DK, et al. Induction of immune responses in patients with B-cell lymphoma against the surface-immunoglobulin idiotype expressed by their tumors. N Engl J Med 1992; 327: 1209–15

    PubMed  CAS  Google Scholar 

  120. Campbell MJ, Carroll W, Kon S, et al. Idiotype vaccination against murine B cell lymphoma. Humoral and cellular responses elicited by tumor derived immunoglobulin M and its molecular subunits. J Immunol 1987; 139: 2825–33

    PubMed  CAS  Google Scholar 

  121. Campbell MJ, Esserman L, Byars NE, et al. Development of a new therapeutic approach to B cell malignancy: the induction of immunity by the host against cell surface receptor on the tumor. Int Rev Immunol 1989; 4: 251–70

    PubMed  CAS  Google Scholar 

  122. Sallusto F, Lanzavecchia A. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granocyte/macrophage colony stimulating factor plus interleukin-4 and downregulated by tumor necrosis factor alpha. J Exp Med 1994; 179: 1109–18

    PubMed  CAS  Google Scholar 

  123. Hsu FJ, Benike C, Fagnoni F, et al. Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nature Med 1996; 2: 52–8

    PubMed  CAS  Google Scholar 

  124. Griffiths AD, Williams SC, Hartley O, et al. Isolation of high affinity human antibodies directly from large synthetic repertoires. EMBO J 1994; 13: 45–60

    Google Scholar 

  125. Lonberg N, Taylor LD, Harding FA, et al. Antigen-specific human antibodies from mice comprising four distinct genetic modifications. Nature 1994; 368: 856–9

    PubMed  CAS  Google Scholar 

  126. Engert A, Gottstein C, Bohlen H, et al. Cocktails of ricin Achain immunotoxins against different antigens on Hodgkin and Sternberg-Reed cells have superior anti-tumor effects against HRS cells in vitro and solid Hodgkin tumors in mice. Int J Cancer 1995; 63: 304–9

    PubMed  CAS  Google Scholar 

  127. Holliger P, Brissinck J, Williams RL, et al. Specific killing of lymphoma cells by cytotoxic T-cells mediated by a bispecific diabody. Protein Eng 1996; 9: 299–305

    PubMed  CAS  Google Scholar 

  128. Shen GL, Li JL, Ghetie MA, et al. Evaluation of four CD22 antibodies as ricin A-chain-containing immunotoxins for the in vivo therapy of human B-cell leukemias and lymphomas. Int J Cancer 1988; 42: 792–7

    PubMed  CAS  Google Scholar 

  129. Stevenson FK, Zhu D, King CA, et al. Idiotypic DNA vaccines against B-cell lymphoma. Immunol Rev 1995; 145: 211–28

    PubMed  CAS  Google Scholar 

  130. Vlasveld LT, Hekman A, Vyth-Dreese FA, et al. Treatment of low-grade non-Hodgkin’s lymphoma with continuous infusion of low-dose recombinant interleukin-2 in combination with the B-cell-specific antibody CLB-CD19. Cancer Immunol Immunother 1995; 40: 37–47

    PubMed  CAS  Google Scholar 

  131. Nadler LM, Stashenko P, Hardy R, et al. Serotherapy of a patient with a monoclonal antibody directed against a human lymphoma associated antigen. Cancer Res 1980; 40: 3147–54

    PubMed  CAS  Google Scholar 

  132. Dillman RO, Beauregard JC, Halpern SE, et al. Toxicities and side effects associated with intravenous infusions of murine monoclonal antibodies. J Biol Response Mod 1986; 5: 73–84

    PubMed  CAS  Google Scholar 

  133. Press OW, Appelbaum F, Ledbetter JA, et al. Monoclonal antibody 1F5 (anti-CD20) serotherapy of human B cell lymphomas. Blood 1987; 69: 584–91

    PubMed  CAS  Google Scholar 

  134. Scheinberg DA, Strauss DJ, Yeh SD, et al. A phase I toxicity, pharmacology, and dosimetry trial of monoclonal antibody OKB7 in patients with non-Hodgkin’s lymphoma: effects of tumor burden and antigen expression. J Clin Oncol 1990; 8: 792–803

    PubMed  CAS  Google Scholar 

  135. Dyer MJS, Hale G, Hayhoe FGJ, et al. Effects of CAMPATH-1 antibodies in vivo in patients with lymphoid malignancies: influence of antibody idiotype. Blood 1989; 73: 1431–9

    PubMed  CAS  Google Scholar 

  136. Knox SJ, Levy R, Hodgkinson S, et al. Observations on the effect of chimeric anti-CD4 monoclonal antibody in patients with mycosis fungoides. Blood 1991; 77: 20–30

    PubMed  CAS  Google Scholar 

  137. Knox S, Hoppe RT, Maloney D, et al. Treatment of cutaneous T-cell lymphoma with chimeric anti-CD4 monoclonal antibody. Blood 1996; 87: 893–9

    PubMed  CAS  Google Scholar 

  138. Miller R, Oseroff AR, Stratte PT, et al. Monoclonal antibody therapeutic trials in seven patients with T-cell lymphoma. Blood 1983; 62: 988–95

    PubMed  CAS  Google Scholar 

  139. Dillman RO, Beauregard JC, Shawler DL, et al. Continuous infusion of T101 monoclonal antibody in chronic lymphocytic leukemia and cutaneous T-cell lymphoma. J Biol Response Mod 1986; 5: 394–9

    PubMed  CAS  Google Scholar 

  140. Waldmann TA, Goldman CK, Bongiovanni KF, et al. Therapy of patients with human T-cell lymphotrophic virus I-induced adult T-cell leukemia with anti-Tac, a monoclonal antibody to the receptor for interleukin-2. Blood 1988; 72: 1805–16

    PubMed  CAS  Google Scholar 

  141. Emilie D, Wijdenes J, Gisselbrecht C, et al. Administration of an anti-interleukin-6 monoclonal antibody to patients with acquired immunodeficiency syndrome and lymphoma: effect on lymphoma growth and on B clinical symptoms. Blood 1994; 84: 2472–9

    PubMed  CAS  Google Scholar 

  142. Vitetta ES, Stone M, Amlot P, et al. Phase-I immunotoxin trial in patients with B-cell lymphoma. Cancer Res 1991; 51: 4052–8

    PubMed  CAS  Google Scholar 

  143. Sausville EA, Headlee D, Stetler-Stevenson M, et al. Continuous infusion of the anti-CD22 immunotoxin IgG-RFB4-SMPT-dgA in patients with B-cell lymphoma: a phase-I study. Blood 1995; 85: 3457–65

    PubMed  CAS  Google Scholar 

  144. Stone MJ, Sausville EA, Fay JW, et al. A phase-I study of bolus vs continuous infusion of the anti-CD 19 immunotoxin, IgG-HD37-dgA in patients with B cell lymphoma. Blood 1996; 88: 1188–97

    PubMed  CAS  Google Scholar 

  145. Conry RM, Khazaeli MB, Saleh M. A phase-I study of murine monoclonal antibody HD37-deglycosylated ricin A-chain in chemotherapy resistant B cell lymphoma [abstract]. Blood 1992; 80: 44a

    Google Scholar 

  146. Grossbard ML, Fidias P. Prospects for immunotoxin therapy of non-Hodgkin’s lymphoma. Clin Immunol Immunopathol 1995; 76: 107–14

    PubMed  CAS  Google Scholar 

  147. Hertler AA, Schlossmann DM, Borowitz MJ, et al. An anti-CD5 immunotoxin for chronic lymphocytic leukemia: enhancement of cytotoxicity with human serum albumin monensin. Int J Cancer 1989; 43: 215–9

    PubMed  CAS  Google Scholar 

  148. LeMaistre CF, Rosen S, Frankel A, et al. Phase I trial of H65-RTA immunoconjugate in patients with cutaneous T-cell lymphoma. Blood 1991; 78: 1173–82

    PubMed  CAS  Google Scholar 

  149. Tepler I, Schwartz G, Parker K, et al. Phase I trial of an interleukin-2 fusion toxin (DAB486IL-2) in hematologic malignancies: complete response in a patient with Hodgkin’s disease refractory to chemotherapy. Cancer 1994; 73: 1276–85

    PubMed  CAS  Google Scholar 

  150. Hesketh P, Caquioa P, Bulger K, et al. Clinical response in cutaneous T-cell lymphoma to an IL-2-diphtheria hybrid toxin (DAB486IL-2) [abstract]. Proc Am Soc Clin Oncol 1992; 11: 1076

    Google Scholar 

  151. Platanias LC, Ratain MJ, O’Brien M, et al. Phase I trial of a genetically engineered interleukin-2 fusion toxin (DAB486IL-2) as a 6 hour intravenous infusion in patients with hematologic malignancies. Leuk Lymphoma 1994; 14: 257–62

    PubMed  CAS  Google Scholar 

  152. Foss FM, Borkowski TA, Gilliom M, et al. Chimeric fusion protein toxin DAB486IL-2 in advanced mycosis fungoides and the Sezary syndrome: correlation of activity and interleukin-2 receptor expression in aphase-II study. Blood 1994; 84: 1765–74

    PubMed  CAS  Google Scholar 

  153. Kaminski M, Fig L, Zasaday K, et al. Phase I evaluation of 131I-MB 1 antibody radioimmunotherapy (RIT) of B-cell lymphoma [abstract]. Blood 1990; 76: 355a

    Google Scholar 

  154. Zimmer AM, Rosen ST, Spies SM, et al. Radioimmunotherapy of patients with cutaneous T-cell lymphoma using an iodine-131-labeled monoclonal antibody: analysis of the retreatment following plasmapheresis. J Nucl Med 1988; 29: 174–80

    PubMed  CAS  Google Scholar 

  155. Rosen ST, Zimmer AM, Goldman-Leikin R, et al. Radioimmunodetection and radioimmunotherapy of cutaneous T-cell lymphomas using an 131I-labeled monoclonal antibody: an Illinois Cancer Council study. J Clin Oncol 1987; 5: 562–73

    PubMed  CAS  Google Scholar 

  156. Waldmann TA, Pastan IH, Gansow OA, et al. The multichain interleukin-2 receptor: a target for immunotherapy. Ann Intern Med 1992; 116: 148–60

    PubMed  CAS  Google Scholar 

  157. Waldmann TA, White JD, Carrasquillo JA, et al. Radioimmunotherapy of interleukin-2Rα-expressing adult T-cell leukemia with yttrium-90-labeled anti-Tac. Blood 1995; 86: 4063–75

    PubMed  CAS  Google Scholar 

  158. Press OW, Eary JF, Badger CC, et al. Treatment of refractory non-Hodgkin’s lymphoma with radiolabeled MB-1 (anti-CD37) antibody. J Clin Oncol 1989; 7: 1027–38

    PubMed  CAS  Google Scholar 

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Schnell, R., Barth, S., Diehl, V. et al. Non-Hodgkin’s Lymphoma. BioDrugs 8, 216–234 (1997). https://doi.org/10.2165/00063030-199708030-00007

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